INTRODUCTION: Incubation of blood with CrSO(4)-coated glass beads stimulates the synthesis of anti-inflammatory cytokines, such as interleukin-1 receptor antagonist (IL-1ra), IL-4, IL-10, and IL-13. As IL-1beta is thought to play a key role in the development of osteoarthritis (OA), this product, also known as Orthokin, might be a viable treatment for symptomatic knee OA. The aim of the current study was to evaluate the efficacy of Orthokin for treatment of symptomatic knee OA in a randomized, multicentre, double-blind, placebo-controlled trial. PATIENTS AND METHODS: One hundred and sixty-seven patients receivedsix intra-articular injections either with Orthokin or physiological saline. The primary efficacy objective consisted of 30% superiority on the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) at 3, 6, 9, and 12 months post-treatment. Additionally, the patients completed the visual analogue scale for pain, the Knee injury and Osteoarthritis Outcome Score (KOOS) and Knee Society Clinical Rating System. RESULTS:Orthokin and placebo treatment resulted in similar improvements on the WOMAC (16.8% vs 16.5%, respectively; n.s.). Orthokin resulted in significantly more improvement for KOOS symptom (P = 0.002) and KOOS sport (P = 0.042) parameters as compared to placebo treatment. For most other outcome parameters, Orthokin-treated patients consistently showed higher improvement compared to placebo-treated patients, although none of these differences were statistically significant. Two serious adverse events were observed in the Orthokin group: one patient with repeated severe inflammatory reactions of the knee joint within hours after the injection and one patient with septic arthritis which was attributed to the injection procedure rather than the product. CONCLUSION: The statistically significant improvement of KOOS symptom and sport parameters together with the consistently higher, though non-statistically significant, improvement of most other parameters demonstrates that Orthokin clearly induces a biological response different from placebo treatment and warrant future investigations into the possible chondroprotective effect of Orthokin. However, in the current study the primary efficacy objective was not met and, therefore, the use of Orthokin currently cannot yet be recommended for the treatment of OA.
RCT Entities:
INTRODUCTION: Incubation of blood with CrSO(4)-coated glass beads stimulates the synthesis of anti-inflammatory cytokines, such as interleukin-1 receptor antagonist (IL-1ra), IL-4, IL-10, and IL-13. As IL-1beta is thought to play a key role in the development of osteoarthritis (OA), this product, also known as Orthokin, might be a viable treatment for symptomatic knee OA. The aim of the current study was to evaluate the efficacy of Orthokin for treatment of symptomatic knee OA in a randomized, multicentre, double-blind, placebo-controlled trial. PATIENTS AND METHODS: One hundred and sixty-seven patients received six intra-articular injections either with Orthokin or physiological saline. The primary efficacy objective consisted of 30% superiority on the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) at 3, 6, 9, and 12 months post-treatment. Additionally, the patients completed the visual analogue scale for pain, the Knee injury and Osteoarthritis Outcome Score (KOOS) and Knee Society Clinical Rating System. RESULTS: Orthokin and placebo treatment resulted in similar improvements on the WOMAC (16.8% vs 16.5%, respectively; n.s.). Orthokin resulted in significantly more improvement for KOOS symptom (P = 0.002) and KOOS sport (P = 0.042) parameters as compared to placebo treatment. For most other outcome parameters, Orthokin-treated patients consistently showed higher improvement compared to placebo-treated patients, although none of these differences were statistically significant. Two serious adverse events were observed in the Orthokin group: one patient with repeated severe inflammatory reactions of the knee joint within hours after the injection and one patient with septic arthritis which was attributed to the injection procedure rather than the product. CONCLUSION: The statistically significant improvement of KOOS symptom and sport parameters together with the consistently higher, though non-statistically significant, improvement of most other parameters demonstrates that Orthokin clearly induces a biological response different from placebo treatment and warrant future investigations into the possible chondroprotective effect of Orthokin. However, in the current study the primary efficacy objective was not met and, therefore, the use of Orthokin currently cannot yet be recommended for the treatment of OA.
Authors: L R Goodrich; J C Grieger; J N Phillips; N Khan; S J Gray; C W McIlwraith; R J Samulski Journal: Gene Ther Date: 2015-04-23 Impact factor: 5.250